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Biomedical subjects

K Kawashima

Publications and source records attributed to K Kawashima.

At least 145 records · Page 8Linked to original sources
PubMed1997

Pharmacological properties of traditional medicines. XXIII. Searching for active compounds in the blood and bile of rats after oral administrations of extracts of sansohnin [symbol: see text].

We made a trial of searching for the bioactive substances from Sansohnin [symbol: see text]. The blood and bile of rats after the oral administration of extracts of Sansohnin were analyzed by three-dimensional high-performance liquid chromatography (3D-HPLC). In blood, spinosin and feruloyl spinosin were found after the oral administration of a butanol extract of Sansohnin. In bile, spinosin and feruloyl spinosin were also identified after the oral administration of a water extract of Sansohnin. Spinosin and feruloyl spinosin induced the prolongation of hexobarbital sleeping time in mice at doses of 50 and 100 mg/kg, respectively. We concluded that spinosin and feruloyl spinosin were the bioactive constituents of Sansohnin. It was assumed that spinosin and feruloyl spinosin circulated through the intestine and liver, therefore, these results will provide support for the sedative and hypnotic use of this crude drug in Oriental medicine.

Administration, Oral↗
PubMed1997

Antihypertensive effect of repeatedly administered YM358, an angiotensin AT1-receptor antagonist, in stroke-prone spontaneously hypertensive rats.

YM358 2,7-diethyl-5-[[2'-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[ 1,5-b][1,2,4]-triazole potassium salt), a novel nonpeptide angiotensin AT1-receptor antagonist, was administered daily for 4 weeks to 24-week-old stroke-prone spontaneously hypertensive rats (SHRSP). Its effects on systolic, mean and diastolic arterial pressure (SAP, MAP and DAP), heart rate and locomotor activity were investigated by using radiotelemetry. A clear diurnal variation in blood pressure, heart rate and locomotor activity was observed in synchrony with the light cycle. YM358 at a daily oral dose of 10 or 30 mg/kg produced a reduction of blood pressure in a dose-dependent manner. Although a mild attenuation of the antihypertensive effect of YM358 was observed during the early stage of therapy, YM358 at 30 mg/kg per day produced a significant and consistent decrease in 24-hr MAP and DAP, and it prevented the further development of hypertension. YM358 did not affect either heart rate or locomotor activity or their diurnal variations. After the discontinuation of therapy with YM358, the blood pressure recovered promptly to the control level while there was no sign of a rebound increase in blood pressure. These results suggest that YM358 may be potentially useful for the treatment of hypertension.

Angiotensin Receptor Antagonists↗
PubMed1997

Domon L, an immunopotentiating agent, acts as an NF-kappaB activator.

Domon L, a heat-treated component of gram-negative bacterium Achromobacter stenohalis, is used for the treatment of infectious diseases of animals. Here, we investigated the immunopotentiating potential of Domon L. In vitro studies showed that Domon L enhanced nitric oxide (NO) formation from murine macrophage RAW264.7 cells in concert with interferon (IFN)-gamma. The effect of Domon L on NF-kappaB activation was investigated, in order to understand the molecular mechanisms of enhanced NO formation by Domon L. Domon L induced translocation of NF-kappaB to the nucleus in RAW264.7 cells. Induction of NF-kappaB dependent gene expression by Domon L was further confirmed using a transfectant containing an NF-kappaB-luciferase reporter gene. In vivo injection of Domon L elevated both serum IL-6 and mucoprotein, whose gene expression is partly under the control of NF-kappaB. The spleen cells of rats treated with Domon L produced much more NO when stimulated with LPS + IFN gamma than spleen cells of untreated rats. These results suggest that Domon L acts as an anti-infectious agent via NF-kappaB activation.

Achromobacter↗
PubMed1997

Cloning and characterization of novel gene, DCRR1, expressed from Down's syndrome critical region of human chromosome 21q22.2.

The new gene, DCRR1, from the proximal part of the Down's syndrome critical region (DCR) was identified by the GRAIL analysis of the 97-kb nucleotide sequence of two P1 DNAs and the cDNA for DCRR1 gene was cloned. A 7.36-kb cDNA encodes the imcompleted open reading frame composed of 1941 amino acid residues (220.2 kDa). The deduced amino acid sequence contains the conserved domain for protein phosphatases at the N-terminus. The domain encoding the rod-like tail of a myosin heavy chain was also found near the C-terminal region besides the signature for an actin binding protein, profilin, suggesting its possible role as a microtuble-associated protein. Two different sizes (7.9 and 9.0 kb) of mRNAs were detected in the poly(A)+ RNA from abundant tissues by the Northern analysis. The smaller transcript was only transcribed at a high level in the testis. The imbalance of the DCRR1 gene dosage may contibute to the pathogenesis of Down's syndrome.

Amino Acid Sequence↗
PubMed1997

[CD7+, CD34+, electronmicroscopically peroxidase-negative acute leukemia transformed from polycythemia vera after 12 years follow-up].

We reported a 72-year-old female patient who developed acute leukemia following a long course of polycythemia vera (PV). For 12 years she had been treated with phlebotomy, nimustine, busulfan, hydroxyurea and irradiation on splenomegaly. In November 1995, her peripheral blood smear showed blast of 30%. Bone marrow blasts were microscopically as well as electromicroscopically peroxidase-negative and CD7 and HLA-DR positive. Six months later, the blasts were positive for CD7, CD34 and HLA-DR. On the basis of morphologic, biochemical and immunophenotypic features, the patient was diagnosed acute leukemia, probably arising at a primitive multipotential stem cell level. She failed to respond to the various combination therapy including prednisolone, vincristine, cytarabine, daunorubicin and etoposide. The stem-cell-leukemia transformation in PV occurs rarely and may be refractory to chemotherapy.

Acute Disease↗
PubMed1997

[Epididymal sarcoidosis: a case report].

A rare case of epididymal sarcoidosis is reported. A 52-year-old man was admitted with a painless mass in the left scrotum. An operation revealed that a 1-cm mass was located at the epididymal head and well demarcated from the testis and the surrounding tissue. Epididymectomy was performed. Histopathological diagnosis was noncaseating granulomas consistent with sarcoidosis. Systemic examination showed bilateral hilar lymphadenopathy and bilateral peripheral anterior synechiae, but these lesions were diagnosed as inactive. Serum level of angiotensin-converting enzyme was normal.

Epididymis↗
PubMed1996

Production of polyclonal antibody specific for human natriuretic peptide receptor B.

Polyclonal antibody against human natriuretic peptide receptor B (NPR-B) was produced using as immunogen a soluble chimeric protein consisting of the extracellular domain of the receptor fused with Fc portion of human IgG. The antibody was purified with protein A column, and then subjected to an adsorption of anti-Fc antibody using IgG column. The purified antibody recognized human NPR-B but not the related receptor NPR-A. The antibody inhibited C-type natriuretic peptide (CNP)-mediated intracellular cGMP accumulation in a dose-dependent manner. With regard to specific activity for the neutralization, the antibody purified with IgG column was significantly stronger than that before the adsorption step, indicating that the purification of the antibody with IgG column was extremely effective to remove the contaminating anti-Fc antibody from anti-NPR-B antibody. Western blot analysis using the purified antibody revealed that while the native NPR-B exists as an oligomer, the truncated NPR-B lacking most of its cytoplasmic domain is a monomer. This finding suggests that the cytoplasmic region may be involved in the oligomerization of the receptor. The results in this study demonstrate that soluble IgG fusion protein is very effective and useful for generating specific antibodies to the proteins expressed on cell surface.

Animals↗
PubMed1996

Activation of transcription factor NF-kappa B in experimental glomerulonephritis in rats.

NF-kappa B plays a pivotal role in cells of the immune system as an inducible transcriptional activator. NF-kappa B regulates the transcription of many genes of pro-inflammatory cytokines and cell adhesion molecules, which could be involved in the pathogenesis of glomerulonephritis. Using a gel shift assay, we investigated NF-kappa B DNA-binding activity in glomeruli of WKY rats injected with nephrotoxic serum (NTS). Kinetic analysis indicated that the NF-kappa B DNA-binding activity in glomeruli, composed of p50 subunit determined by a supershift assay, increased on day 1 after NTS injection and the maximal activation was observed on day 3 to 5. NF-kappa B activation persisted at least until day 14. Pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-kappa B activation, inhibited the NTS-induced increase of glomerular NF-kappa B DNA-binding activity, followed by the inhibition of mRNA expression of IL-1 beta, MCP-1, ICAM-1 and iNOS, which are known to be regulated by NF-kappa B. PDTC also prevented urinary protein excretion which is a pathophysiological parameter for glomerulonephritis. These results suggest that NF-kappa B activation causes the induction of pro-inflammatory factors in nephritic glomeruli, which may play significant roles in the pathogenesis of glomerulonephritis.

Animals↗
PubMed1996

Localization and synthesis of acetylcholine in human leukemic T cell lines.

In order to clarify the origin of acetylcholine (ACh) in human blood, we measured the content and synthesis activity of ACh in several human leukemic cell lines. The intracellular ACh content determined by a specific and sensitive radioimmunoassay in the human leukemic T cell lines, HSB-2, MOLT-3, and CEM, was 79.6, 36.2, and 9.5 pmol/10(6) cells, respectively. These values were 9-70-fold higher than those of other cell lines, including a helper T cell line, Jurkat. Stimulation of HSB-2 and MOLT-3 by phytohemagglutinin (PHA) increased both the intracellular content and release of ACh into the culture medium, but did not influence the intracellular content and release of ACh in CEM. ACh synthesis activity was found in all the T cell lines tested. Bromoacetylcholine (100 microM), a choline acetyltransferase (ChAT) inhibitor, and bromoacetyl-L-carnitine (100 microM), a carnitine acetyltransferase (CarAT) inhibitor, decreased ACh-synthesizing activity in MOLT-3, and HSB-2 and CEM, by about 50% and 30%, respectively, indicating that both ChAT, and to a lesser extent CarAt, are involved in ACh synthesis in T cells. These results suggest that T lymphocytes have the potential to synthesize and release ACh, which may play a role in regulating T cell-dependent immune responses.

Acetylcholine↗
PubMed1996

Structure of the 5'-flanking regulatory region of the mouse gene encoding the clearance receptor for atrial natriuretic peptide.

A full-length cDNA, encoding the mouse atrial natriuretic peptide clearance receptor (ANP-CR), was isolated from a mouse lung cDNA library. The deduced amino acid sequence of the mouse ANP-CR, showing a typical tripartite organization which lacks a guanylyl cyclase domain, was extremely well conserved compared with the ANP-CR homologs. To understand the molecular mechanisms underlying the regulation of mouse ANP-CR gene expression and to define the essential DNA sequences for the transcriptional activity, a genomic clone containing over 9 kb of the 5'-flanking region of the mouse ANP-CR gene has been isolated from a mouse genomic library. Sequence analysis revealed that the 2.3-kb region upstream from an ATG codon of the mouse ANP-CR gene contained a number of putative regulatory elements; TATA box, CAAT box, cAMP response element, AP-1 and two shear stress responsive elements. Additionally, an unusual feature was the presence of the tandem-repeated AP-2-like elements, which were closely overlapped with SP-1 element. Promoter analysis using deletion plasmids in mouse Balb/3T3 cells, highly producing ANP-CR mRNA, demonstrated that deletion of the sequence from -144 to +46 relative to the transcription start point caused a dramatic decrease of the transcriptional activity and that the TATA box at -269 was not essential for the basal transcriptional activity. Primer extension analysis indicated that transcription of the mouse ANP-CR gene starts from at least two major sites, suggesting that the sequence from -144 to +46, which was shown to involve a novel sequence composed of tandem-repeated TATA-box-like elements, contained promoter sequences. Furthermore, cis-acting negative elements were shown to be situated in three regions (from -1178 to -708, from -707 to -625 and from -248 to -145) of the mouse ANP-CR gene promoter.

Amino Acid Sequence↗
PubMed1996

Effect of KCA-098 on the function of osteoblast-like cells and the formation of TRAP-positive multinucleated cells in a mouse bone marrow cell population.

KCA-098 (3,9-bis(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinol ine-6-one), an analogue of coumestrol (a naturally occurring weak phytoestrogen), dose-dependently increased alkaline phosphatase activity of osteoblastic ROS 17/2.8 cells and freshly-isolated osteoblasts from neonatal mouse calvaria, and reduced cell proliferation. In addition, KCA-098 increased the synthesis of collagenese-digestible protein (CDP) of ROS 17/2.8 cells. On the other hand, KCA-098 had no effect on the basal synthesis of osteocalcin but reduced the 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)(2)D3)-induced increase in osteocalcin synthesized by ROS 17/2.8 cells. Therefore, KCA-098 had a bidirectional effect on the differentiation of osteoblasts (i.e., stimulating both alkaline phosphatase activity and synthesis of CDP and inhibiting osteocalcin synthesis). However, as KCA-098 stimulated the mineralization of chick embryonic bone in organ culture and recovered the bone density reduced by ovariectomy of rats, it would serve overall to stimulate the differentiation of osteoblasts. On the other hand, KCA-098 inhibited the formation of tartrate-resistant, acid phosphate-positive multinucleated cells (TRAP(+)MNC) induced by 1 alpha,25(OH)(2)D(3), parathyroid hormone (PTH), and prostaglandin E2 (PGE2) in cultures of mouse bone marrow cells, showing that it inhibits the formation of osteoclast-like cells. Coumestrol and 17beta-estradiol had no effect on the proliferation and alkaline phosphatase activity of ROS 17/2.8 cells. They did, however, dose-dependently inhibit osteoclast-like cell formation as well as KCA-098 did, indicating that the main action of coumestrol and 17beta-estradiol on bone tissue is the inhibition of bone resorption.

Acid Phosphatase↗
PubMed1996

Changes of lymphocyte subpopulations in pigs infected with porcine reproductive and respiratory syndrome (PRRS) virus.

Abnormal changes of T-cell subpopulation were observed in the peripheral blood lymphocytes of pigs infected with porcine reproductive and respiratory syndrome (PRRS) virus. Pigs with naturally occurring PRRS revealed increases in CD2+ and CD8+ cells, and decreases in CD4+ cells and the ratios of CD4+/CD8+ cells. Specific-pathogen-free pigs inoculated with PRRS virus showed remarkable decreases in total lymphocytes, CD4+ and CD2+ cells on Postinoculation Day (PID) 3. The decline of CD4+ cells continued for at least 14 days, while CD2+ cells showed a tendency to increase thereafter. On the other hand,CD8+ cells slightly decreased in number on PID 3, and then increased remarkably; their number was significantly larger on PIDs 28 and 35 than on PID 0. The ratios of CD4+/CD8+ cells were significantly low between PIDs 3 and 28 as compared with PID 0. However, there were no differences in thymocyte subpopulations between infected and non-infected pigs, suggesting that the PRRS virus does not modulate intrathymic T-cell differentiation. In an experiment with peripheral blood mononuclear cell cultures, PRRS virus caused neither alteration of T-cell subpopulations nor cell proliferation, suggesting that the virus is not cytotoxic for CD4+ cells and not mitogenic for CD8+ cells.

Animals↗
PubMed1996

Viral antigen and B and T lymphocytes in lymphoid tissues of gnotobiotic piglets infected with hog cholera virus.

Four 4-day-old gnotobiotic piglets infected intranasally with the Kanagawa/74 strain of hog cholera virus (HCV) did not develop severe illness over a period of 3 weeks. Large amounts of HCV were isolated from the lymphoid tissues and serum at necropsy. After the acute phase, hyperplasia of histiocytes and plasmacytopoiesis were observed in two pigs (killed 14 and 21 days after inoculation). The number of CD4+ and CD8+ T lymphocytes increased significantly and their location was consistent with the site of HCV replication. The results suggest that a CD8+ T-lymphocyte reaction is associated with persistent HCV infection.

Acute Disease↗
PubMed1996

Detection of porcine reproductive and respiratory syndrome virus and Mycoplasma hyorhinis antigens in pulmonary lesions of pigs suffering from respiratory distress.

Eleven field cases of a disease characterized by severe dyspnoea or abdominal breathing were examined post mortem. The affected pigs had antibody against porcine reproductive and respiratory syndrome virus (PRRSV). The predominant lung lesions were severe proliferative and interstitial pneumonia, and slight suppurative bronchopneumonia. The lesions were closely associated with the sites at which PRRSV and Mycoplasma hyorhinis antigens were detected. Four of five pigs inoculated with PRRSV developed slight pneumonitis. The fifth animal, which died of severe pneumonitis, yielded a heavy culture of M. hyorhinis. These findings demonstrate that dual infection with M. hyorhinis and PRRSV caused severe pulmonary lesions.

Animals↗
PubMed1996

Interpretation of scintigraphy of papillary cystadenoma lymphomatosum (Warthin's tumor) on the basis of histopathologic findings.

OBJECTIVES: The accumulation of 99mTc-pertechnetate in Warthin's tumor was estimated scintigraphically and histopathologically to determine the role of the epithelial component in scintigraphy. STUDY DESIGN: Six cases underwent histopathologic examination and scintigraphic evaluation with 99mTc-pertechnetate. Histopathologically the tumors were classified into types according to the epithelial component and cystic space and compared with scintigraphic results evaluated by dynamic radioactive index and wash-out image. RESULTS: Histopathologic and scintigraphic observations showed an adequate correlation. Cases with a large epithelial component and poor cystic space showed a large radioactive index of dynamic scintigraphy and hot accumulation of wash-out image. CONCLUSION: The scintigraphic results were chiefly due to the epithelial component, but the influence of the cystic space could not be disregarded.

Adenolymphoma↗
PubMed1996

Facial contouring surgery with the scapular osteo-adipo-fascial flap.

Recently, deepithelialized scapular or parascapular flaps have been used for reconstruction of facial contour. The authors used a scapular osteo-adipo-fascial flap, based on the subscapular vascular system, accompanied with scapular bone on the angular branch, for surgical correction of facial contour in two cases. At follow-up, both patients showed aesthetic improvements, and were pleased with the results. The scapular osteo-adipo-fascial flap provides a technique to reconstruct facial contour, including the bony structure as well as the soft tissue.

Adult↗
PubMed1996

Effect of repeated administration of KT3-671, a nonpeptide AT1 receptor antagonist, on diurnal variation in blood pressure, heart rate, and locomotor activity in stroke-prone spontaneously hypertensive rats as determined by radiotelemetry.

KT3-671, a nonpeptide AT1 receptor antagonist, was administered to 20-week-old stroke-prone spontaneously hypertensive rats (SHRSP) daily for 3 weeks. Its effects on systolic, mean, and diastolic arterial blood pressure (SAP, MAP, DAP), heart rate and locomotor activity were investigated with radiotelemetry. A clear diurnal variation in blood pressure, heart rate, and locomotor activity was observed in synchrony with the light cycle. KT3-671 at a daily dose of 10 mg/kg orally (p.o), produced a significant and consistent reduction in blood pressure, preventing the development of hypertension. KT3-671 reduced SAP more than DAP, suggesting that it may affect both vascular tone and cardiac output. Although KT3-671 did not affect diurnal rhythms in heart rate and locomotor activity, it did cause a slight but significant reduction in heart rate. The MAP determined 23 h after the administration of KT3-671 showed a significant reduction from the day 2 of therapy to the day 3 after discontinuation of therapy, suggesting a long duration of antihypertensive action. There was no rebound increase in blood pressure after discontinuation of KT3-671 therapy. These results suggest that KT3-671 may be potentially useful in the therapy of hypertension.

Angiotensin Receptor Antagonists↗